Fluid filled ampoules and methods for their use in aerosolizers

ABSTRACT

A fluid filled ampoule comprises an ampoule body having a top end, a bottom end and a sealed interior containing a liquid. A top tab is coupled to the top end and is removable to create a drain vent in the top end. A bottom tab is coupled to the bottom end and is removable to create a drain opening in the bottom end. A movable shroud is coupled to the top end and is disposed about the top tab. The shroud is movable to permit access to the top tab.

This application is a continuation application of U.S. Ser. No.09/812,755, filed Mar. 20, 2001, the complete disclosures of which areherein incorporated by reference.

BACKGROUND OF THE INVENTION

This invention relates generally to the field of liquid aerosolization,and in particular to the management of liquids used in theaerosolization process. More specifically, the invention relates toampoules containing liquids that are to be aerosolized.

The ability to aerosolize or nebulize small liquid droplets is importantto a variety of industries. Merely by way of example, manypharmaceuticals can now be delivered to the lungs in liquid form.Aerosolization is also a useful technique to dispense deodorizers,perfumes, insecticides or the like into the atmosphere.

Aerosolizers or nebulizers typically utilize a supply of liquid that iscontained in some type of reservoir, such as a container, canister, orthe like. In this way, the liquid may be stored in a sealed environmentuntil ready for aerosolization, However, because the liquid is sealedwithin a container, the fluid needs to be removed and transferred to theaerosol generator prior to aerosolization. Hence, this invention relatesto the use of various ampoules that are employed to store liquids priorto aerosolization, as well as to techniques for accessing andtransferring the liquid to an aerosol generator.

BRIEF SUMMARY OF THE INVENTION

In one embodiment, a fluid filled ampoule is provided that comprises anampoule body having a top end, a bottom end, and a sealed interiorcontaining a liquid. The ampoule body may be manufactured by blowing orvacuum forming the ampoule body in a mold. The ampoule body may then befiled with liquid, and a melt sealing process may be used to seal theliquid within the ampoule body. The ampoule further includes a top tabthat is coupled to the top end and a bottom tab that is coupled to thebottom end. In this way, the top tab may be removed to create a drainvent in the top end while the bottom tab may be removed to create adrain opening in the bottom end. Conveniently, the top and bottom tabsmay be removed by twisting the tabs. Alternatively, the tabs may becrack tabs where material is not completely removed but the seal isbroken. Combinations of twist and crack tabs may also be used. Further,in one alternative, the ampoule may be constructed to be pierced ateither the top end and/or the bottom end to create the vent or drainopening.

In one aspect, the ampoule may include a shroud that is coupled to thetop end so that it is disposed about the top tab. In this way, the toptab is prevented from being removed until first moving or bending theshroud away from the top tab. Such a shroud is useful in ensuring theproper order of removal of the top and bottom tabs. For example, bypreventing access to the top tab, a user may be trained to first removethe bottom tab. Once removed, the ampoule may then be placed into anaerosolization device. In so doing, the liquid remains within theampoule because no vent has yet been provided. When the ampoule iswithin the aerosolization device, the shroud may be bent and the top tabremoved to create the vent opening. Upon creation of the vent opening,the liquid flows into the aerosolization device where it is availablefor aerosolization.

In another aspect, the ampoule may include one or more orientationelements to ensure proper orientation of the ampoule when it is insertedinto an aerosolization device. For example, the ampoule body may includea pair of longitudinal rails that are adapted to guide the ampoule intoa receiver of an aerosolization device. Conveniently, the rails may havedifferent sizes so that the ampoule may be inserted into the receiver inonly one orientation.

In a further aspect, the ampoule may include one or more keying elementsthat are used to ensure that the correct ampoule is used in anaerosolization device. The keying elements may be used to preventinsertion of the ampoule into an aerosolization device if the ampoule isnot the correct ampoule. Such keying elements may include, for example,one or more protrusions that extend from the ampoule body. Theseprotrusions must fit within corresponding slots within theaerosolization device to permit the ampoule to be inserted.Alternatively, the keying element may be configured to prevent operationof the aerosolization device unless recognized by the aerosolizationdevice. For example, the ampoule body may include a readable pattern,such as a bar code, a magnetic pattern, or the like, which must berecognized by the aerosolization device before operation will bepermitted. In another aspect, the ampoule may include one or moreprotrusions to trigger an electrical switch which closes a circuit inthe aerosol generator. Such a trigger may be used to supply power to theaerosol generator. When the user inhales, a flow sensor may be actuatedto fully power up the aerosol generator to aerosolize the liquid. If thecorrect protrusions are not included on the ampoule, the aerosolgenerator will not actuate.

In a further aspect, the ampoule may be provided with a large sealingsurface that is configured to provide a seal with the aerosol generator.The large sealing surface is advantageous in that it leaves a relativelylarge, empty socket in the aerosolization device after the ampoule isremoved. In this way, the aerosolization device may more easily beaccessed during cleaning after the ampoule has been removed. The largesealing surface may conveniently be provided by tapering the bottom endto increase the surface area. In yet another aspect, the ampoule isprovided with a relatively thick wall to reduce the chance of dropletspillage. For example, the ampoule body may be provided with a wallthickness of at least about 0.03 inches.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of one embodiment of an ampoule accordingto the invention.

FIG. 2 is a front view of the ampoule of FIG. 1.

FIG. 3 is a side view of the ampoule of FIG. 1.

FIG. 4 is a bottom-end view of the ampoule of FIG. 1.

FIG. 4A is a cross-sectional side view of the ampoule of FIG. 4 takenalong lines A—A.

FIG. 4B is a cross-sectional side view of the ampoule of FIG. 4 takenalong lines B—B.

FIG. 5 is a bottom-end view of the ampoule of FIG. 1 after the removalof a bottom tab to expose a drain opening.

FIG. 6 is a side view of the ampoule of FIG. 5 and further illustratingthe removal of a top tab to expose a vent opening.

FIG. 7 is a top view of the ampoule of FIG. 6 and further illustratingthe bending of a shroud to gain access to the top tab (shown removed).

FIG. 8 is a perspective view of an alternative ampoule according to theinvention.

FIG. 9 is a perspective view of an ampoule having contact points thatserve as keying element according to the invention.

FIG. 10 illustrates another embodiment of an ampoule having contactfingers that are used as keying elements according to the invention.

DESCRIPTION OF THE SPECIFIC EMBODIMENTS

The invention provides various ampoules used to store liquids that areto be atomized as well as techniques for transferring the stored liquidsto an aerosolizer. The ampoules of the invention may convenientlyinclude a variety of features to facilitate their use within varioustypes of aerosolization devices. Such features may include, for example,features to insure their proper insertion into an aerosolization device,to insure proper operation of the ampoules when releasing the storedliquids, and to insure that the correct ampoule is being inserted intothe aerosolization device.

The ampoules of the invention may be used with a wide variety ofaerosolization devices that are configured to aerosolize a volume ofliquid. Such aerosolizers may be of the type, for example, where avibratable member is vibrated at ultrasonic frequencies to produceliquid droplets. Some specific, non-limiting examples of technology forproducing fine liquid droplets is by supplying liquid to an apertureplate having a plurality of tapered apertures and vibrating the apertureplate to eject liquid droplets through the apertures. Such a techniqueis described generally in U.S. Pat. Nos. 5,164,740; 5,938,117;5,586,550; 5,758,637 and 6,085,740, the complete disclosures of whichare herein incorporated by reference. However, it will be appreciatedthat the invention is not intended to be limited for use only with suchdevices.

The ampoules of the invention may be used to store a wide variety ofliquids. Merely by way of example, liquids that may be stored within theampoules include various pharmaceuticals such as saline, albuterol,chromatin, budesinide, nicotine, THC, cocaine, and the like. Otherliquids that may be stored include insecticides, deodorizers, perfumes,and the like. Hence, it will be appreciated that the ampoules of theinvention may be used to store essentially any type of liquid that iscapable of being aerosolized.

The ampoules of the invention may be constructed by blowing orvacuum-forming the ampoule in a mold, filling the ampoule with liquid,and melt-sealing the liquid into the ampoule. The ampoules may furtherbe provided with a set of removable tabs to provide a drain vent and adrain opening. Typically, these will be located in the top and bottom ofthe ampoule so that the liquid may drain by force of gravity once theopenings are formed. The tabs may be removed by twisting, cracking, orthe like so that the opening may be formed. In some cases, the ampoulesmay be configured to be opened simply by piercing the top and/or bottomend. Such piercing elements may conveniently be incorporated into theaerosolization device.

Various materials may be used to construct the ampoules, such asmoderate durometer polymer materials, thermoplastic synthetics, such aslow density polyethylene and polypropylene, and the like. The ampoulesmay be provided with a thick enough wall to minimize droplet spillage.For instance, the wall thickness may be greater than about 0.030 inch.The ampoule may further be configured so that the diameter of the drainopening minimizes the drip potential for the fluid stored within theampoule. For example, larger diameter openings may be provided whenstoring higher viscosity fluids and smaller diameter openings may beused for low viscosity fluids.

The ampoules may include one or more orienting elements to ensure properorientation of the ampoule when inserted into an aerosolization device.For example, the ampoule may include one or more keyed rails that mustbe inserted into the appropriate slots in the aerosolization device. Oneway to key the rails is by making them of different widths so that eachrail must be inserted into a specific slot in the aerosolization device.Conveniently, the difference in width may be accomplished by thickeningthe entire length, or by the incorporation of one or more discretepoints of thicknesses, which may be either at the top, bottom or anycombination of points along the length of the rail. The use of discretewidth increases in the rails is advantageous in that it decreases theaddition of voids in the fill space and thus reduces the hold-up volumeof the ampoule when drained.

Another feature of the ampoules is that they may include in theirphysical design an order of operation. In other words, the ampoule maybe configured so that it is operated in a certain way when removing theliquid. For example, the first twist-off tab to be used may beunrestricted and easily accessible to the user. On the other hand,access to the second twist-off tab may be prevented access until a prioroperation, such as the folding of a shroud, is performed in order toexpose the second twist-off tab.

The use of a folding shroud may also be used as a handle for removal ofthe ampoule after drainage of the fluid. Such a handle may also be usedto place the ampoule into the space in which it is loaded in theaerosolization device.

Another feature of the ampoules is that they may be provided with alarge sealing surface as well as a large ratio of the sealing surface tothe twist-off tab for the drain opening. The sealing surface may beprovided with a large diameter so that the empty socket which remainsafter the ampoule is removed may easily be cleaned. The seal between theampoule and the aerosolization device may be made between the outsidediameter of the ampoule and the inside diameter of a receiver in theaerosolization device. However, this seal may also made between theinside of the ampoule and the outside of the aerosolization devicereceiver.

In another embodiment, the ampoule may be constructed so that it may notbe used with some aerosolization devices, or so that it may fit withinmore than one device. For example, the ampoule may include male orfemale protrusions that may be used to key the ampoule to a specificaerosolization device or devices. The presence of such a keying featureon the aerosolization device receiver would require the same key featureto be on the ampoule. However, some ampoules with the same pattern, buta different number of keying protrusions or intrusions may be acceptedby multiple front ends of aerosolization devices. An ampoule may beconfigured to be excluded or included into a specific aerosolizationdevice by choosing the number and/or location of the keying protrusionsor inclusions.

The ampoules may alternatively be provided with a variety of otherkeying features, such as by using a thin metallic strip that is attachedto the side or face of the ampoule. For example, the strip may be bondedto the ampoule, molded into the ampoule, or crimped onto the side of theampoule after production. The strip may have a series of alternatingmetallic areas where a reader in the aerosolization device may read thepattern on the surface through a resistance method to identify the typeof drug in the ampoule, the expiration date, the dosage to be delivered,or any other information that may accompany the ampoule. As anotheralternative, the ampoule may be bar coded with visible, ultraviolet, orinfrared ink to provide the same keying features through a detectormounted within the aerosolization device. Such aerosolization devicesmay utilize a memory device, a magnetic strip, or other communicationdevice to communicate the specifics of the ampoule to the aerosolizationdevice. The controller of the aerosolization device may also beconfigured to provide feedback, to keep a tally of the total dosestaken, or other information.

A further alternative for keying the ampoule may be to provideprotrusions molded into the side of the ampoule on the keying rail.These protrusions or nubs may either stick out in line with the planemade by the two side rails or may be mounted 90 degrees relative to thisplane. The side rails may be of different widths, and of differentoverall lengths, as well as shapes that are different from each other orthat are different from other ampoules. The rail may have a variety ofshapes, such as square, rounded, triangular, angled, or the like, andmay also be applied to the overall volume of the ampoule for a uniquekeying strategy.

Such protrusions may be used to close an electromechanical circuit wheninserted into the aerosolization device. Once the circuit is closed,power is provided to the aerosol generator. For example, the aerosolgenerator may be placed in sleep or silent mode. When the user inhales,a flow sensor senses the breath and increases the power to the aerosolgenerator to aerosolize the liquid.

Referring now to FIGS. 1–4, one embodiment of an ampoule 10 will bedescribed. Ampoule 10 comprises an ampoule body 12 having a top end 14and a bottom end 16. Ampoule body 12 has a sealed interior 18 containinga liquid 20 (see FIGS. 4A and 4B). Ampoule body 12 may be constructed byblowing or vacuum-forming the ampoule body in a mold. The ampoule bodymay then be filled with liquid 20 and a melt-sealing process used toseal the fluid within ampoule body 10.

Integrally formed with ampoule body 12 at top end 14 is a top tab 22that is surrounded by a bendable shroud 24. Tab 22 is removable fromampoule body 12 by grasping tab 22 and twisting it relative to ampoulebody 12. Once tab 22 is removed, a drain vent 26 is formed in top end 14as best shown in FIG. 7. To permit tab 22 to be twisted off, shroud 24is bent relative to ampoule body 12 as illustrated generally in FIG. 7.Conveniently, recesses 28 may be provided in shroud 24 to facilitatebending of shroud 24 to provide access to tab 22.

Integrally formed with ampoule body 12 at bottom end 16 is a bottom tab30 to form a drain opening 32 as best shown in FIG. 5. Conveniently,bottom tab 30 may be configured to be twisted off in a manner similar totop tab 22 to form drain opening 32.

When both drain vent 26 and drain opening 32 are formed, liquid 20 ispermitted to drain through drain opening 32 by force of gravity(assuming top end 14 is vertically above bottom end 16). In use, ampoule10 may need to be inserted into an aerosolization device. Conveniently,the aerosolization device may include a receiver into which ampoule 10is inserted. Merely by way of example, ampoule 10 may be inserted into areceiver as described in co-pending U.S. application Ser. No.09/812,987, filed on the same date as the present application, thecomplete disclosure of which is herein incorporated by reference.Ampoule 10 is configured to ensure the proper order of tab removal whenusing ampoule 10 with an aerosolization device. For example, shroud 24prevents access to top tab 22, thereby suggesting to the user that tab30 should first be removed in order to create the drain opening. Oncetab 30 is removed, ampoule 10 may be inserted into an aerosolizationdevice, with liquid being prevented from exiting through drain opening32 by the vacuum existing within interior 18. Once within the device,shroud 24 may be bent to the side and top tab 22 twisted off to providedrain vents 26. In so doing, liquid 20 is free to flow from ampoule body12 and into the aerosolization device where it may be aerosolized.

Bottom end 16 includes an outer edge 34 that is used to form a sealbetween ampoule body 12 and the aerosolization device into which ampoule10 is inserted. Outer edge 34 has a relatively large diameter so thatthe socket into which ampoule 10 is inserted is also relatively large.In this way, the empty socket in the aerosolization device may easily becleaned following removal of ampoule 10. Merely by way of example, outeredge 34 may have a diameter in the range from about 0.2 inch to about 1inch.

Ampoule body 12 includes a pair of longitudinal rails 36 and 38. As bestshown in FIG. 4, rail 36 is thicker than rail 38. In this way, rails 36and 38 are keyed to ensure proper orientation of ampoule 10 into anaerosolization device. For example, the aerosolization device mayinclude a receiver having a wide slot and a narrow slot that areconfigured to receiver rails 36 and 38, respectively.

Ampoule further includes a set of keying protrusions 40 that protrudefrom ampoule body 12. Protrusions 40 are used to key ampoule 10 so thatit may be inserted only into aerosolization devices that arespecifically configured to receive such an ampoule. For example, asshown, ampoule 10 includes four protrusions 40. With such aconfiguration, the aerosolization device may include four slots that areconfigured to receive protrusions 40. The slots have the same dimensionand are at the same angle of orientation so that ampoule 10 may beinserted into the aerosolization device. To vary the keying features,ampoule 10 may be provided with a different number of protrusions, or bychanging the size and/or position of protrusions 40 on ampoule body 12.In this way, ampoule 10 may be keyed for a specific device. With such aconfiguration, a drug may be placed into ampoule 10 which isspecifically configured for a certain aerosolization device. If theampoule containing the proper drug is not inserted into theaerosolization device, the drug may not be aerosolized. Although shownwith protrusions, it will be appreciated that a wide variety of otherkeys may be used to key ampoule 10 as previously described. Further,other specific examples of keying features will be described hereinafterwith reference to FIGS. 9 and 10.

As shown in FIGS. 2 and 6, various information may be molded intoampoule body 12. For example, the lot number of the ampoule and theexpiration date of the drug may be molded into ampoule body 12. Further,it will be appreciated that other descriptive information may also beincluded on ampoule body 12.

Shown in FIG. 8 is an alternative embodiment of an ampoule 50. Ampoule50 is essentially identical to ampoule 10 except for the size of variouscomponents. For convenience of illustration, similar components will bereferred to using the same reference numerals followed by a prime (“′”).Ampoule body 12′ of ampoule 50 is significantly smaller than ampoulebody 12. In this way, ampoule 50 may be used for drugs requiring less ofa unit dosage. Because ampoule body 12′ has been reduced in size, toptab 22′ and shroud 24′ are made larger so that ampoule 50 retains thesame overall size as ampoule 12. In this way, a variety of ampoules thatcontain different unit dosages may be used within the same type ofaerosolization devices. Merely by way of example, ampoule 50 may beconfigured to hold a volume of about 0.2 mL to about 1.0 mL whileampoule 10 may hold a volume of about 0.2 mL to about 6 mL, and morepreferably from about 0.8 mL to about 3.0 mL. For other aerosolizationapplications, such as when aerosolizing a deodorizer or insecticizer,larger volumes may be used.

FIG. 9 illustrates an alternative embodiment of an ampoule 52. Ampoulecomprises an ampoule body 54 having a top end 56 and a bottom end 58.Ampoule body 54 includes a reservoir 60 that contains a liquid. Ampoulebody 54 includes score lines 62 that permit bottom end 58 to be brokenoff from ampoule body 54 to provide a drain opening, and score lines 63to permit top end 56 to be broken off to provide a vent. Conveniently, apiercing mechanism may be used to pierce reservoir 60 to permit theliquid to drain from reservoir 60.

Ampoule body 54 further includes a side 64 that includes a series ofalternating metallic areas 66. In this way, when ampoule 52 is insertedinto an aerosolization device, an electrical reader may be used to readthe pattern of metallic areas 66 to determine the liquid containedwithin reservoir 66. If the appropriate ampoule has not been inserted,the aerosolization device may include a controller to prevent itsoperation. Although shown in connection with FIG. 9, it will beappreciated that similar metallic areas may be used within any of theembodiments described herein in order to key the ampoule to a specifictype of liquid.

FIG. 10 illustrates an alternative embodiment of an ampoule 68 that hasthe same overall appearance to ampoule 52 of FIG. 9. For convenience ofdiscussion, similar elements will be referred to with the same referencenumerals. Ampoule 68 differs from ampoule 52 in that it utilizes a setof fingers 70 that serve as keying elements to identify the particulartype of liquid contained within reservoir 60. Ampoule 68 may be usedwithin an aerosolization device having spring contact leaves that areactuated to cause a circuit to be created upon insertion. In this way,the aerosolization device recognizes the specific type of ampoule andmay be configured to operate only when the proper ampoule has beeninserted.

Other techniques for keying such ampoules is by including a metal filmon the surface of the ampoule body. This may be accomplished by plating,spraying, taping or any other attachment scheme. The attached metal maybe selectively covered by paint or may be attached only in certainareas. The presence of the metal serves as a conductor and patterns ofthe conductive material may cause the aerosolization device torecognizes the particular type of ampoule. For example, the pattern ofconductive areas may be sensed by a linear or other set of springsensors. Such spring tension sensors may serve to both hold the ampoulein place and to push the contacts against the ampoule body to make areliable contact. Such a scheme may be used with any of the ampoulesdescribed herein.

In some embodiments, the ampoule may be provided with a programmablememory chip, such as an EPROM chip that is on the surface or embedded aspart of the manufacturing process. The aerosolization device may includea reader to read the information from the memory. In this way, theaerosolizer may keep a record of various information, such as the numberof doses, the time of dosing, the expiration date, and the like.

The invention has now been described in detail for purposes of clarityof understanding. However, it will be appreciated that certain changesand modifications may be practiced within the scope of the appendedclaims.

1. A method for supplying liquid to an aerosolization device, the methodcomprising: providing an ampoule comprising an ampoule body having a topend, a bottom end, and a sealed interior containing a liquid, and an airvent disposed near the top end; creating a drain opening in the bottomend; inserting the ampoule into a receiving portion of theaerosolization device; separately opening the air vent; wherein uponopening of the air vent and the creation of the drain opening, theliquid in the interior flows out of the drain opening and into theaerosolization device where it is available for aerosolization by theaerosolization; and wherein the ampoule further includes at least onekeying element on the ampoule body, and further comprising inserting theaerosolization device and permitting operation of the aerosolizationdevice only when the keying element is accepted by the aerosolizationdevice.
 2. A method as in claim 1, further comprising inserting theampoule into the aerosolization device after creating the drain openingand prior to opening the drain vent.
 3. A method as in claim 1, whereinthe ampoule includes a top tab that is removable to form the air ventand a shroud that is disposed about the top tab, and further comprisingbending the shroud to move the shroud away from the top tab.
 4. A methodas in claim 3, wherein the bottom end includes a bottom tab that isremovable to create the drain opening, and further comprising twistingthe top tab and the bottom tab to remove them from the ampoule body. 5.A method as in claim 1, wherein the ampoule further includes a pair oflongitudinal rails on the ampoule body, and further comprising insertingthe ampoule into the aerosolization device such that the rails arereceived into corresponding slots in the aerosolization device.
 6. Amethod as in claim 5, wherein the rails and the slots have differentsizes, and further comprising inserting the ampoule such that the railsand received into the appropriately sized slots.
 7. A method as in claim2, wherein the bottom end is tapered, and further comprising providing aseal with the bottom end and the aerosolization device.
 8. A method asin claim 1, wherein the keying element comprises a protrusion on theampoule body, and further comprising inserting the ampoule into theaerosolization device such that the protrusion is received into a keyedslot in the aerosolization device.
 9. A method as in claim 1, whereinthe liquid comprises a medicament.
 10. A method for supplying liquid toan aerosolization device, the method comprising: providing an ampoulecomprising an ampoule body having a top end, a bottom end, and a sealedinterior containing a liquid, and an air vent disposed near the top end;creating a drain opening in the bottom end; inserting the ampoule into areceiving portion of the aerosolization device; separately opening theair vent; wherein upon opening of the air vent and the creation of thedrain opening, the liquid in the interior flows out of the drain openingand into the aerosolization device where it is available foraerosolization by the aerosolization device; and wherein the ampoulefurther includes a pair of longitudinal rails on the ampoule body, andfurther comprising inserting the ampoule into the aerosolization devicesuch that the rails are received into corresponding slots in theaerosolization device.